Alverine Research Articles

Clinical efficacy of compound alverine citrate in treatment of functional abdominal pain syndrome

Clinical efficacy of compound alverine citrate in treatment of functional abdominal pain syndrome

Inclusion of a Spasmolytic in Bowel Cleansing

The quality of colon cleansing and the tolerance of patients to the procedure are two major determinants of the quality of a colonoscopy. Many bowel-cleansing regimens are known, but there is no ideal regimen. Alverine citrate (Relaxyl, Spasmonal) is a spasmolytic agent that has been shown to affect responses of mechanoreceptors of the intestine to both mechanical and chemical stimuli. Patients who underwent colonoscopies at four centers were randomly assigned two different bowel-cleansing procedures. The bowel-cleansing methods were oral sodium phosphate (NaP) (Group I) and oral NaP plus alverine citrate (Group II). Patients were randomized into one of these regimens. The quality of colon cleansing was assessed by an endoscopist with an empirical, clinically meaningful 3-point scale. Both groups were similar with respect to age, gender, and pre- and postcolonoscopic diagnosis. In Group I, 76 patients (47 women and 29 men; aged 39.53 ± 7.87 years) and in Group II, 71 patients (41 women and 30 men; aged 39.78 ± 8.27 years) were included in the study. In Groups I and II, 37 (48.7%) and 41 (57.7%) patients had perfect bowel cleansing, respectively. The overall colon cleansing in the group with NaP plus alverine citrate was comparable with that in the NaP group. The tolerability of patients to the colonoscopy in the two groups was also similar. Based on the present data, adding oral alverine citrate to NaP does not increase either the quality of bowel cleansing or the tolerance of patients to the procedure.

A rapid and most sensitive liquid chromatography/tandem mass spectrometry method for simultaneous determination of alverine and its major metabolite, para hydroxy alverine, in human plasma: application to a pharmacokinetic and bioequivalence study

A rapid and highly sensitive method for the determination of alverine (ALV) and its metabolite, para hydroxy alverine (PHA), in human plasma using LC-MS/MS in positive ion electrospray ionization (ESI) in multiple reactions monitoring (MRM) mode was developed and validated. The procedure involves a simple solid phase extraction (SPE). Chromatographic separation was carried out on a Hypersil GOLD C(18) column (50 mm x 4.6 mm, 5 microm) with an isocratic mobile phase and a total run time of 1.5 min. The standard calibration curves showed excellent linearity within the range of 0.060-10.051 ng/mL for ALV and 0.059-10.017 ng/mL for PHA (r > or = 0.990). This method was successfully applied to a pharmacokinetic study after oral administration of alverine citrate 120 mg capsule in Indian healthy male volunteers.

Liquid Chromatography/Tandem Mass Spectrometry for the Simultaneous Determination of Alverine and its Metabolite, Monohydroxy Alverine, in Human Plasma: Application to a Pharmacokinetic Study

A rapid and sensitive LC‐MS‐MS method for the determination of alverine (ALV) and its major metabolite, monohydroxy alverine (MHA), in human plasma using imipramine as an internal standard was developed and validated. The analytes were extracted from 0.5 mL aliquots of human plasma by solid phase extraction, using oasis cartridge. Chromatographic separation was carried on Thermo Gold C18 column (50 × 4.6 mm, 5 μ) at 30 °C, with isocratic mobile phase, a flow rate of 0.4 mL/min and a total run time of 3.5 min. Detection and quantification were performed using a mass spectrometer in the selected reaction‐monitoring mode with positive electrospray ionization at m/z 282.3 → 91.11 for alverine, m/z 298.3 → 106.9 for mono‐hydroxy‐alverine, and m/z 281.0 → 86.0 for internal standard (IS) respectively. This assay was linear over a concentration range of 0.060‐10 ng/mL with a lower limit of quantification of 0.060 ng/mL for both alverine and monohydroxy alverine. The coefficient of variation for the assay precision were <9.18% and <8.44%, the accuracy were >104.66% and >100.38% for alverine and monohydroxy alverine respectively. This method was successfully applied to a pharmacokinetic study after oral administration of alverine citrate 60 mg capsule in healthy male subjects.

Alverine citrate, simeticone, and Rome III irritable bowel syndrome

Alverine citrate, simeticone, and Rome III irritable bowel syndrome

Rectal antinociceptive properties of alverine citrate are linked to antagonism at the 5-HT1A receptor subtype.

Serotonin (5-HT) is considered as a major mediator causing hyperalgesia and is involved in inflammatory reactions and irritable bowel syndrome. Alverine citrate may possess visceral antinociceptive properties in a rat model of rectal distension-induced abdominal contractions. This study was designed to evaluate the pharmacological properties of alverine citrate in a rat model of rectal hyperalgesia induced by 5-HTP (5-HT precursor) and by a selective 5-HT1A agonist (8-OH-DPAT) and to compare this activity with a reference 5-HT1A antagonist (WAY 100635). At 4 h after their administration, 5-HTP and 8-OH-DPAT increased the number of abdominal contractions in response to rectal distension at the lowest volume of distension (0.4 mL). When injected intraperitoneally before 8-OH-DPAT and 5-HTP, WAY 100635 (1 mg kg(-1)) blocked their nociceptive effect, but also reduced the response to the highest volume of distension (1.6 mL). Similarly, when injected intraperitoneally, alverine citrate (20 mg kg(-1)) suppressed the effect of 5-HTP, but not that of 8-OH-DPAT. However, when injected intracerebroventricularly (75 microg/rat) alverine citrate reduced 8-OH-DPAT-induced enhancement of rectal distension-induced abdominal contractions. In-vitro binding studies revealed that alverine citrate had a high affinity for 5-HT1A receptors and a weak affinity for 5-HT3 and 5-HT4 subtypes. These results suggest that 5-HTP-induced rectal hypersensitivity involves 5-TH1A receptors and that alverine citrate acts as a selective antagonist at the 5-HT1A receptor subtype to block both 5-HTP and 8-OH-DPAT-induced rectal hypersensitivity.

Clinical trial: the efficacy of alverine citrate/simeticone combination on abdominal pain/discomfort in irritable bowel syndrome ‐ a randomized, double‐blind, placebo‐controlled study

Alverine citrate and simeticone combination has been used for almost 20 years in irritable bowel syndrome (IBS), but supportive scientific evidence of efficacy was limited. To evaluate the efficacy of alverine citrate and simeticone combination in patients with IBS-related abdominal pain/discomfort. A total of 412 IBS patients meeting ROME III criteria were included in this double-blind randomized placebo-controlled study if their abdominal pain/discomfort intensity was at least 60 mm on a 0-100 mm visual analogue scale (VAS) during a 2-week run-in treatment-free period. Patients were randomly assigned through the use of Interactive Voice Response System to receive either alverine citrate 60 mg with simeticone 300 mg three times daily or matching placebo for 4 weeks. The full analysis set included 409 patients (71.4% female: mean age: 46.2 +/- 13.9 years). At week 4, alverine citrate and simeticone group had lower VAS scores of abdominal pain/discomfort (median: 40 mm vs. 50 mm, P = 0.047) and higher responder rate (46.8% vs. 34.3%, OR = 1.3; P = 0.01) as compared with placebo group. Patient receiving alverine citrate and simeticone reported greater global symptom improvement compared with those receiving placebo (P = 0.0001). Reported adverse events were similar in both groups. Alverine citrate/simeticone combination was significantly more effective than placebo in relieving abdominal pain/discomfort in patients with IBS.

A case report of alverine-citrate-induced acute hepatitis

Alverine citrate is one of the most commonly used antispasmodic drugs for patients with irritable bowel syndrome. Alverine-citrate-induced hepatotoxicity is extremely rare, with only a few cases having been reported worldwide. We present a case of a 75-year-old female patient who experienced complicated jaundice and abdominal discomfort after taking alverine citrate. Other causes of hepatitis were ruled out and the results of the liver function test returned to normal after ceasing the drug. This is the first case report in Korea of alverine-citrate-induced hepatotoxicity.

Evaluation on clinical therapeutic efficacy of compound alverine citrate and clostridium butyricum on irritable bowel syndrome

Objective To observe and evaluate the efficacy of compound alverine citrate with capsule of clostridium butyricum live in the treatment of IBS. Methods 81 patients with IBS were divided into 2 groups randomly. Patients in group A (41 cases) were treated orally with capsule of compound alverine citrate (Meteospasmyl, one capsule, 3 times a day) and capsule of clostridium butyricum live (Ataining, 1.26, twice a day),while those in group B (40 cases) were given orally pinaverium bromide (Dicetel, 50 mg, 3 times a day) for 4 weeks. A observation and evaluation on the change of such symptoms as abdominal pain, abdominal bulge, diarrhea, or constipation was performed respectively at the end of 2nd and 4th week of therapeutic period. Results The total effective rates were 70.7% and 88.6% at the end of 2nd and 4th week of the medication period respectively in group A, and those in group B were 65.0% and 81.8% simultaneously. There was no significant difference (P>0.05) between the efficacy of group A and B, neither after 2 weeks' treatment nor after 4 weeks' treatment. However, at 2nd week, the improvement of abdominal bulge symptom in group A was better than in group B (P<0.01). Conclusions Compound alverine citrate and capsule of clostridium butyricum live can be used in the treatment of IBS with a definite therapeutic effect. Key words: Compound alverine citrate; Meteospasmyl; Clostridium butyricum; Pinaverium bromide; Irritable bowel syndrome

Validated LC–MS/MS method for determination of Alverine and one of its hydroxy metabolites in human plasma along with its application to a bioequivalence study

The present research work involves a first of its kind rapid and sensitive liquid chromatography–tandem mass spectrometry (LC–MS/MS) method developed and validated for simultaneous analysis of Alverine (ALV) and one of its hydroxy metabolites, para hydroxy Alverine (PHA) in human plasma. The analytes were extracted from the matrix using a simple solid-phase extraction procedure. Mebeverine was used as the internal standard for both analytes. A Kromasil C8 column provided chromatographic separation of analytes followed by detection with mass spectrometry. The method involves simple isocratic chromatography conditions and mass spectrometric detection in the positive ionization mode using an API 5000 MS/MS system. The proposed method has been validated with a linear range of 100–10,000 pg/mL for both ALV and PHA. The interrun and intrarun precision values are within 6.3%, 3.7% for ALV and 6.3%, 3.2% for PHA at LOQ levels. The intrarun accuracy in terms of % RE was within the range of −7.0% to −0.1% and −8.1% to −1.7% for ALV and PHA, respectively whereas the interrun accuracy was within the range of −5.1% to −0.5% for ALV and −8.6% to 0.4% for PHA, respectively. The overall recoveries for ALV and PHA were 83.5% and 86.2% respectively. Total elution time was about 4 min which allowed quantitation of more than 150 plasma samples per day. This validated method was used successfully for analysis of real samples from a bioequivalence study.

Evolving mechanisms of action of alverine citrate on phasic smooth muscles

We have investigated the mechanisms underlying the paradoxical ability of the antispasmodic, alverine, to enhance spontaneous activity in smooth muscles while suppressing evoked activity. The effects of alverine on spontaneous and induced contractile activity were examined in preliminary experiments with various smooth muscles. More detailed effects were also investigated by recording membrane potential, intracellular Ca2+ concentration ([Ca2+]i) and tension from single-bundle detrusor smooth muscle (DSM) of the guinea-pig urinary bladder. Alverine (10 microM) increased the frequency and amplitude of spontaneous action potentials, transient increases in [Ca2+]i and associated contractions. Alverine also decreased action potential rate of decay, suggesting inhibition of L-type Ca channel inactivation. Charybdotoxin (50 nM) but neither cyclopiazonic acid (10 microM) nor Bay K 8644 (10 microM) attenuated alverine-induced enhancement of spontaneous contractions. Alverine suppressed contractions produced by high K (40 mM) or ACh (10 microM), without affecting electrical responses and with little suppression of increases in [Ca2+]i. This feature was very similar to that of the effects of the Rho kinase inhibitor Y-27632 (10 microM). Alverine may increase Ca influx during action potentials due to inhibition of the inactivation of L-type Ca channels, but may also suppress evoked activity by inhibiting the sensitivity of contractile proteins to Ca2+. The proportional contribution of Ca-dependent and Ca-independent contractions in DSM may differ between spontaneous and evoked activity, necessitating further investigations into the interactions between these pathways for assessing the therapeutic potential of alverine to treat DSM dysfunction.

Syndrome de l'intestin irritable : options thérapeutiques actuelles

Relieving abdominal pain is the principal treatment objective for patients with irritable bowel syndrome. No single drug stands out in the treatment strategy for this illness. Antispasmodics, magnesium aluminum silicates, and alverine citrate drugs all remain initial options for treatment, although their prescription is impeded by the fact that an increasing number are no longer approved for reimbursement. Increased dietary fibers often have a harmful effect on symptoms. Some patients are probably intolerant to some foods but there is no satisfactory proof on which to base a restrictive diet. Improved knowledge of the pathophysiology of irritable bowel syndrome has made it possible to diversify treatments that act first on one of the key pathophysiologic elements, visceral hypersensitivity. Antidepressants (especially tricyclics) can be used at low doses. Among the serotonergic drugs, serotonin 5-HT4 receptors agonists (tegaserod) may be available soon, but the development of 5-HT3 antagonists (alosetron, cilansetron) has been stopped for safety reasons (ischemic colitis and severe constipation). Non-drug options such as hypnosis, psychotherapy, relaxation, or yoga, may also be proposed to some patients. Probiotics are a possible treatment in the future.

Effects of alverine citrate on cat intestinal mechanoreceptor responses to chemical and mechanical stimuli.

Alverine citrate is commonly used in the treatment of painful affections of the colon. To determine whether alverine citrate acts on the vagal sensory endings. Unitary recordings were performed at the level of the vagal fibres in the nodose ganglion of anaesthetized cats using extracellular glass microelectrodes, and the patterns of response to chemical and mechanical stimuli applied to identified vagal intestinal mechanoreceptors were studied. The intestinal mechanoreceptors located at the endings of type C vagal fibres responded mainly to mechanical stimuli (distension and contraction), but also responded to chemical substances (cholecystokinin and substance P). The most conspicuous effect of alverine (2 mg/kg) was that it significantly inhibited the pattern of vagal activity produced in response to either cholecystokinin (5-10 microg/kg), substance P (5-10 microg/kg) or phenylbiguanide (5-10 microg/kg), a 5-HT3 receptor agonist. On the other hand, the unitary vagal response to the mechanical distension was slightly enhanced by alverine, as was any spontaneous activity present. Based on the present data, alverine citrate can be said to decrease the sensitivity of the intestinal mechanoreceptors, which is consistent with its previously established anti-spasmodic effects.

Dyclonine and alverine citrate enhance the cytotoxic effects of proteasome inhibitor MG132 on breast cancer cells

Proteasome is an important target in cancer therapy. To enhance the efficacy of proteasome inhibitors is a challenging task due to the paucity of understanding the functional interactions between proteasome and other cellular pathways in mammalian cells. Taking advantage of the knowledge gained from Saccharomyces cerevisiae, we show that dyclonine and alverine citrate, the major components of two over-the-counter medicines, can substantially enhance the cytotoxic effects of proteasome inhibitor MG132 on breast cancer cells. This study also highlights an important yeast genetic approach to identification of potential therapeutics that can be used for combination therapy with proteasome inhibitors.

A general practice study to compare alverine citrate with mebeverine hydrochloride in the treatment of irritable bowel syndrome

International Journal of Clinical PracticeVolume 40, Issue 7 p. 276-278 Clinical Study A general practice study to compare alverine citrate with mebeverine hydrochloride in the treatment of irritable bowel syndrome G J Tudor MB ChB, G J Tudor MB ChB General Practitioner Radcliffe, ManchesterSearch for more papers by this author G J Tudor MB ChB, G J Tudor MB ChB General Practitioner Radcliffe, ManchesterSearch for more papers by this author First published: 01 July 1986 https://doi.org/10.1111/j.1742-1241.1986.tb07977.xRead the full textAboutRelatedInformationPDFPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessClose modalShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. Volume40, Issue7July 1986Pages 276-278 RelatedInformation RecommendedAlosetron relieves pain and improves bowel function compared with mebeverine in female nonconstipated irritable bowel syndrome patients Jones, Holtmann, Rodrigo, Ehsanullah, Crompton, Jacques, Mills, Alimentary Pharmacology & TherapeuticsIrritable Bowel SyndromeChung Owyang, Textbook of Gastroenterology, [1]Irritable Bowel SyndromeAlexander C Ford, Paul Moayyedi, Nicholas J Talley, Evidence‐Based Gastroenterology and Hepatology, [1]Mebeverine alters small bowel motility in irritable bowel syndromeP. R. EVANS, Y.-T. BAK, J. E. KELLOW, Alimentary Pharmacology & TherapeuticsSubtypes of irritable bowel syndrome on Rome III criteria: A multicenter studyXin Yao, Yun Sheng Yang, Li Hong Cui, Ka Bing Zhao, Zhen Hua Zhang, Li Hua Peng, Xu Guo, Gang Sun, Jun Shang, Wei Feng Wang, Jia Feng, Qiyang Huang, Journal of Gastroenterology and Hepatology

Sterculia bulk-forming agent with smooth-muscle relaxant versus bran in diverticular disease.

Sterculia with and without a smooth-muscle relaxant (alverine citrate) had similar beneficial effects on constipation and reduced the transit times in diverticular disease. Intracolonic pressure, however, varied with the preparation used. Though both preparations relieved the symptoms of diverticular disease, the one containing alverine citrate was more effective. Part of the mode of action of bran may be to relax the smooth muscle of the gut, since its actions were more comparable to those of sterculia plus alverine citrate than to those of sterculia alone.

The effects of alverine citrate on smooth muscle

The effects of alverine citrate on smooth muscle

Qualitative and quantitative tests for alverine citrate

Provisional, unofficial monographs are developed by the Drug Standards Laboratory, in cooperation with the manufacturers of the drug concerned, for publication in the Journal of Pharmaceutical Sciences. The ready availability of this information affords discriminating medical and pharmaceutical practitioners with an added basis for confidence in the quality of new drug products generally, and of those covered by the monographs particularly. Such monographs will appear on drugs representing new chemical entities for which suitable identity tests and assay procedures are not available in the published literature. The purity and assay limits reported for the drugs and their dosage forms are based on observations made on samples representative of commercial production and are considered to be reasonable within expected analytical and manufacturing variation.